The effect of the triblock co-polymer, Pluronic P123 (PP123) on the growth of succinic acid crystals from aqueous solutions is reported at two batch process scales: 10 mL and 350 mL. The presence of small quantities of PP123 is shown to modify the crystal morphology from plate-like crystals to block-like crystals, in a fully reproducible manner. Increasing the quantity of polymer present, or the concentration of succinic acid used, produces needle-like crystals that are less favorable for processing. In-line process analytical tools (FBRM, PVM and Raman) were implemented for the larger volume batch processes, allowing the crystallization to be monitored in real-time. The effect of the polymer on the metastable zone width (MSZW) has also been determined in designing the crystallization experiments and is presented. In addition, the effect of the individual blocks of the co-polymer, poly(ethylene glycol) and poly(propylene glycol) on the crystal morphology was examined and these findings, together with face indexing and knowledge of the underlying crystal structure, have allowed a possible mechanism to be constructed for the interaction of the polymer with the crystal surface. This mechanism is supported by subsequent re-crystallization experiments following washing of the block-like crystals with a non-polar solvent.

Crystal size and shape can be manipulated to enhance the qualities of the final product. In this work the steady-state shape and size of succinic acid crystals, with and without a polymeric additive (Pluronic P123) at 350 mL, scale is reported. The effect of the amplitude of cycles as well as the heating/cooling rates is described, and convergent cycling (direct nucleation control) is compared to static cycling. The results show that the shape of succinic acid crystals changes from plate- to diamond-like after multiple cycling steps, and that the time required for this morphology change to occur is strongly related to the type of cycling. Addition of the polymer is shown to affect both the final shape of the crystals and the time needed to reach size and shape steady-state conditions. It is shown how this phenomenon can be used to improve the design of the crystallization step in order to achieve more efficient downstream operations and, in general, to help optimize the whole manufacturing process.

The design and development of a mesoscale flow reactor is presented, together with initial performance evaluation. The custom-designed KRAIC (kinetically regulated automated input crystallizer) uses liquid-segmented flow to achieve plug flow and mixing throughout the reactor length while helping prevent encrustation issues experienced by other precipitation reactors and crystallizers. Evaluation of the reactor for production of solid-state particle products has been carried out using cooling crystallization of fast growing succinic acid to explore the potential of the KRAIC design to mediate blocking caused during the precipitation process. The segmented flow environment is successful in preventing encrustation during an unseeded 2 h cooling crystallization experiment.